Skip Navigation

Disease in a Dish Approach Could Aid Huntington's Disease Discovery Efforts

September 5, 2014

Media Contacts

Lisa Newbern, 404-727-7709, lisa.newbern@emory.edu

Creating induced pluripotent stem cells or iPS cells allows researchers to establish “disease in a dish” models of conditions ranging from Alzheimer’s disease to diabetes. Scientists at Yerkes National Primate Research Center, Emory University have now applied the technology to a model of Huntington’s disease (HD) in transgenic nonhuman primates, allowing them to conveniently assess the efficacy of potential therapies on neuronal cells in the laboratory.

The results were published this week in Stem Cell Reports.

“A highlight of our model is that our progenitor cells and neurons developed cellular features of HD such as intranuclear inclusions of mutant Huntingtin protein, which most of the currently available cell models do not present,” says senior author Anthony Chan, PhD, DVM, associate professor of human genetics at Emory University School of Medicine and Yerkes National Primate Research Center. “We could use these features as a readout for therapy using drugs or a genetic manipulation.”

Chan and his colleagues were the first in the world to establish a transgenic nonhuman primate model of HD. HD is an inherited neurodegenerative disorder that leads to the appearance of uncontrolled movements and cognitive impairments, usually in adulthood. It is caused by a mutation that introduces an expanded region where one amino acid (glutamine) is repeated dozens of times in the huntingtin protein.

The non-human primate model has extra copies of the huntingtin gene that contains the expanded glutamine repeats. In the non-human primate model, motor and cognitive deficits appear more quickly than in most cases of Huntington’s disease in humans, becoming noticeable within the first two years of the monkeys’ development.

First author Richard Carter, PhD, a graduate of Emory’s Genetics and Molecular Biology doctoral program, and his colleagues created iPS cells from the transgenic monkeys by reprogramming cells derived from the skin or dental pulp. This technique uses retroviruses to introduce reprogramming factors into somatic cells and induces a fraction of them to become pluripotent stem cells. Pluripotent stem cells are able to differentiate into any type of cell in the body, under the right conditions.

The iPS cells were then further induced to become neural progenitor cells and then differentiated neurons. The iPS-derived neural cells developed intracellular and intranuclear aggregates of the mutant huntingtin protein, a classic sign of Huntington’s pathology, as well as an increased sensitivity to oxidative stress.

The sensitivity to oxidative stress was a useful indicator; it could be ameliorated in cell culture, either by a RNA-based gene knockdown approach, or the drug memantine, which is currently being investigated for Huntington’s disease in a human clinical trial.

“We tested two known interventions, but our findings are a proof of principle that this system could be a valuable tool for the discovery and evaluation of other therapies,” Chan says.

The research was supported by the National Institutes of Health’s Office of Research Infrastructure Programs (5R24OD010930 and primate centers: P51OD11132 – formerly NCRR P51RR000165).

Established in 1930, the Yerkes National Primate Research Center paved the way for what has become the National Institutes of Health-funded National Primate Research Center (NPRC) program. For more than eight decades, the Yerkes Research Center has been dedicated to conducting essential basic science and translational research to advance scientific understanding and to improve human health and well-being. Today, the Yerkes Research Center is one of only eight NPRCs. The center provides leadership, training and resources to foster scientific creativity, collaboration and discoveries, and research at the center is grounded in scientific integrity, expert knowledge, respect for colleagues, an open exchange of ideas and compassionate, quality animal care.

Within the fields of microbiology and immunology, neurologic diseases, neuropharmacology, behavioral, cognitive and developmental neuroscience, and psychiatric disorders, the center’s research programs are seeking ways to: develop vaccines for infectious and noninfectious diseases; understand the basic neurobiology and genetics of social behavior and develop new treatment strategies for improving social functioning in social disorders such as autism; interpret brain activity through imaging; increase understanding of progressive illnesses such as Alzheimer’s and Parkinson’s diseases; unlock the secrets of memory; treat drug addiction; determine how the interaction between genetics and society shape who we are; and advance knowledge about the evolutionary links between biology and behavior.


The Robert W. Woodruff Health Sciences Center of Emory University is an academic health science and service center focused on missions of teaching, research, health care and public service. Its components include the Emory University School of Medicine, Nell Hodgson Woodruff School of Nursing, and Rollins School of Public Health; Yerkes National Primate Research Center; Winship Cancer Institute of Emory University; and Emory Healthcare, the largest, most comprehensive health system in Georgia. Emory Healthcare includes: The Emory Clinic, Emory-Children's Center, Emory University Hospital, Emory University Hospital Midtown, Wesley Woods Center, and Emory University Orthopaedics & Spine Hospital. The Woodruff Health Sciences Center has a $2.5 billion budget, 17,600 employees, 2,500 full-time and 1,500 affiliated faculty, 4,700 students and trainees, and a $5.7 billion economic impact on metro Atlanta.

Learn more about Emory’s health sciences: http://emoryhealthblog.com -
@emoryhealthsci (Twitter) - http://emoryhealthsciences.org

###